Comparative pharmacokinetics of chlorogenic acid in beagles after oral administrations of single compound, the extracts of Lonicera japanica, and the mixture of chlorogenic acid, baicalin, and Forsythia suspense

Figures & data

Table 1. Sex and weight of beagles.

No.	A	B	C	D	E	F
Sex	♀	♂	♀	♂	♂	♀
Weight (kg)	9.6	11.2	9.0	11.0	9.2	10.4

Table 2. Administration order.

Group
circle	A	B	C	D	E	F
1	T1^b	R^a	T2^c	T1^b	T2^c	R^a
2	R^a	T2^c	T1^b	T2^c	R^a	T1^b
3	T2^c	T1^b	R^a	R^a	T1^b	T2^c

^a R-reference: 60 mg/kg ChA contained in extracts of Lonicerae japonicae flos (containing 99.8% ChA).

^b T1-test 1:60 mg/kg ChA contained in extracts of Lonicerae japonicae flos (containing 99.8% ChA) + 12 mg/kg extracts of Forsythia suspense vahl (containing 1.4% forsythin and 9.0% forsythoside)+6 mg/kg extracts of Scutellaria baicalensis georgi (containing 97% baicalin).

^c T2-test 2: 60 mg/kg ChA contained in extracts of Lonicerae japonicae flos (containing 37.23% ChA).

Table 3. Accuracy and precision of ChA in plasma samples.

Added concentration (μg/mL)	Mean measured concentration (μg/mL)	Accuracy (%)	RSD (%)
Intraday (n = 6)
25.84	25.69	99.4	1.44
6.46	6.36	98.5	1.64
0.808	0.814	100.7	4.33
0.404	0.412	102.0	8.91
Interday (n = 24)
25.84	25.815	99.9	2.47
6.46	6.55	101.4	3.00
0.808	0.793	98.1	5.26
0.404	0.412	102.0	8.96

Table 4. Accuracy and precision of ChA in urine samples.

Added concentration (μg/mL)	Mean measured concentration (μg/mL)	Accuracy (%)	RSD (%)
Intraday (n = 6)
129.2	126.8	98.1	0.69
12.92	12.34	95.5	2.44
6.46	6.216	96.2	5.72
1.292	1.321	102.2	4.10
Interday (n = 24)
129.2	135.0	104.5	4.53
12.92	12.21	94.5	2.42
6.46	5.97	92.4	5.35
1.292	1.361	105.3	4.87

Table 5. Accuracy and precision of ChA in faeces samples.

Added concentration (μg/mL)	Mean measured concentration (μg/mL)	Accuracy (%)	RSD (%)
Intraday (n = 6)
129.2	128.4	99.4	0.23
12.92	13.17	101.9	2.1
1.292	1.276	98.8	3.75
0.646	0.677	104.8	2.94
Interday (n = 24)
129.2	128.7	99.6	1.35
12.92	12.97	100.4	3.59
1.292	1.206	93.3	6.48
0.646	0.665	102.9	6.66

Table 6. Stability of ChA in beagle plasma under various storage conditions (Mean ± SD, n = 3).

Nominal conc. (μg/mL)	4 °C/4 h (extracted sample)	Room temp./3 h	−20 °C/3 freeze/thaw cycles	−20 °C/1 mon
25.840	102.75 ± 0.35	94.97 ± 1.34	98.69 ± 2.76	114.28 ± 0.99
6.460	103.64 ± 1.78	93.22 ± 1.18	97.16 ± 4.62	103.12 ± 0.34
0.808	100.50 ± 8.03	96.48 ± 0.16	98.88 ± 4.68	107.79 ± 7.90

Table 7. Stability of ChA in beagle urine under various storage conditions (Mean ± SD, n = 3).

Nominal conc. (μg/mL)	4 °C/8 h (extracted sample)	Room temp./6 h	−70 °C/3 freeze/thaw cycles	−70 °C/20 d
129.2	99.87 ± 0.38	99.84 ± 0.13	102.69 ± 0.69	96.78 ± 1.06
12.92	101.27 ± 0.92	100.28 ± 1.60	103.87 ± 1.25	100.65 ± 1.24
6.46	99.80 ± 0.78	102.17 ± 2.00	109.80 ± 14.79	101.32 ± 3.94

Table 8. Stability of ChA in beagle faeces under various storage conditions (Mean ± SD, n = 3).

Nominal conc. (μg/mL)	4 °C/8 h (extracted sample)	Room temp./6 h	−70 °C/3 freeze/thaw cycles	−70 °C/7 d
129.2	101.11 ± 1.22	87.18 ± 1.50	96.43 ± 4.06	99.88 ± 1.69
12.92	101.04 ± 1.16	86.17 ± 2.13	96.18 ± 1.07	98.62 ± 1.34
1.292	91.37 ± 1.93	105.12 ± 11.35	100.41 ± 2.78	101.46 ± 3.21

Figure 1. Concentration–time curve in beagle plasma.

Table 9. Pharmacokinetics parameters for ChA (n = 6).

	R	T1	T2
t1/2 (h)	0.911 ± 0.187	1.094 ± 0.193	1.204 ± 0.309^a
Cmax (μg/mL)	2.350 ± 0.483	2.332 ± 0.606	1.655 ± 0.576^a
Tmax (h)	1.861 ± 0.499	1.833 ± 0.279	1.000 ± 0.459^a
AUC0-t (μg·h/mL)	5.591 ± 1.406	5.325 ± 1.341	3.792 ± 1.794^a
AUC0-∞ (μg·h/mL)	6.324 ± 1.853	6.074 ± 1.473	4.216 ± 1.886^a
F (%)		96.0	66.7

^a p < 0.05, compared with R, T2 has statistical significance.